Experiments were conducted to ascertain whether nonspecific host defenses could be enhanced in a reliable animal model simulating the local bacterial infection that frequently complicates surgical wounds. The test lesion was studied in detail and exemplifies the concept that the ultimate expression of the host-pathogen interaction is the capacity of that pathogen to persist or grow in a given host. Mice were challenged by intramuscular insertion of cotton suture impregnated with 10(7) to 10(8) Escherichia coli K-12. The mice were subsequently killed at intervals, and the suture and muscle mass were retrieved, homogenized, and quantitatively cultured. Numbers of viable organisms in tissue from control animals were compared with those from experimental animals that received BCG (Bacillus Calmette-Guérin) vaccine, a nonspecific immunostimulant, prior to bacterial challenge. Improved tissue antibacterial activity appeared in animals that had received BCG vaccine 13 days prior to bacterial challenge. Differing doses and intervals were not protective. Enhancement of nonspecific host defense mechanisms may be helpful in combination with current measures for improved control of surgical wound infection.